Thebainone-A enol methyl ether

Codeine [i] on heating in alcohol with [319-23] or without [324] acid, with [319-21] or without [322-4] hydrogen, in the presence of noble metal catalysts, undergoes rearrangement to dihydrocodeinone [xiv]. The yields claimed for the transformation are up to 95 per cent. [323], but Rapoport [304] was unable to obtain yields in excess of 50 per cent. Thebadnone-A [xxxvn] is a by-product in this reaction, and can be made the main product by modifying the conditions [325] (cf. the conversion of codeine methyl ether to thebainone-A enol methyl ether by sodium ethoxide). 

Catalytic or sodium and alcohol reduction of thebainone-A enol methyl ether [vi] affords a substance initially allotted the structure [ix] as it is different from an isomeric substance obtained by the catalytic reduction of dihydrotbebaine- >, at that time believed to be [n] [3]. It is now clear that this base is in fact dihydrothebainone A°-enol methyl ether [x] and is formed from [vi] by 1 4-addition of hydrogen to the conjugated system. The product of catalytic reduction of dihydrothebaine- must therefore be the isomeric AB-enol methyl ether [ix] produced by saturation of the 8 14-double bond of [iv]. Bentley, Robinson, and Wain [5] have in this way obtained a base different from that obtained by Small and Browning [3], but believe their product is the true dihydrothebainone-A5-enol methyl ether [ix] as it can also be prepared in 98 per cent, yield by the sodium and liquid ammonia reduction of dihydrothebaine [xi] [5]. 

Dihydrothebainone [xn] or its A6-enol methyl ether [x] is produced in considerable quantity in all reductions of thebaine even under mild conditions, and cannot arise from further reduction of dihydrothebaine. It undoubtedly arises from 1 6-reduction of the conjugated system to give thebainone-A enol methyl ether [vi], which then suffers further 1 4-reduction to dihydrothebainone A6-enol methyl ether [x], the latter boing hydrolysed in acid solution to dihydrothebainone [xn]. This mechanism was suggested by SchOpf and Winterhalder [14], but Small... 

When thebaine [i] is reduced by sodium and boiling alcohol [1-3], or best by sodium in liquid ammonia [4-5], scission of the 4 5-oxygen bridge occurs with the addition of two atoms of hydrogen and production of a phenolic dihydrothebaine, for which the name dihydrothe-baine-< has now been adopted [5]. The sodium-ammonia reduction is rapid, simple, and results in excellent yields of product. Reduction of thebaine with lithium aluminium hydride also yields a phenolic base, /3-dihydrothebaine, which is isomeric with dihydrothebaine- [6], Dihydrothebaine- was first allotted the structure [n] on the basis of its reactions [3], and 3-dihydrothebaine the structure [m] with the abnormal configuration at C-14 on the basis of its hydrolysis to ]S-thebainone-A [iv] [6] thebainone-A enol methyl ether [m] with the normal configuration at C-14, which results from the isomerization of codeine methyl ether [v] under the influence of hot sodium ethoxide, is known to give thebainone-A [rv, C-14 epimer] on hydrolysis [3]. 

Thebainone-A enol methyl ether [m] can be reduced catalytically or with sodium and alcohol to dihydrothebainone A6-enol methyl ether [xi] [3, 12] (erroneously given the A5 structure [rx] at first [3]) and from the catalytic reduction dihydrothebainol-6-methyl ether, identical with the compound obtained from /3-dihydrothebaine, is also obtained [12]. The fact that tliebainono-A onol methyl other and /3-dihydrothebaine... 

Thebainone-A enol methyl ether gives thebainone-A on hydrolysis so readily that no salts of the enol ether can be prepared even in anhydrous media [3]. 

Thebainone-A can also be prepared by the catalytic rearrangement of codeine [vi] under the influence of palladized charcoal at 80° C. [2] by the hydrolysis of thebainone-A enol methyl ether [vn] (prepared by the rearrangement of codeine methyl ether on heating with sodium ethoxide) [3] by the hydrolysis of /j-ethylthiocodide [vm] (obtained by the action of sodium ethoxide on bromo- or /3-chlorocodide) [4-8] (see Chap. XVII) and, in small amount, by the hydrolysis of dihydrothe-baine- [iv] [3]. 

No enol ether of /3-thebainone-A epimeric with thebainone-A enol methyl ether [vn] has been prepared /3-dihydrothebaine was first thought to be such a compound [16] but subsequently was shown to have the structure [hi] [17]. 

This enol ether [xxxi] is the product of catalytic or sodium amalgam reduction of thebainone-A enol methyl ether [vn] [3], from which it arises by 1 4-addition of hydrogen to the conjugated system, and it can also be prepared by the hydrogenation of thebaine in neutral solution [3]. It is very readily hydrolysed to dihydrothebainone, which doubtless arises from this during the reduction of thebaine in acid solution. (Dihydrothebainone was prepared by Speyer and Ereunds [10] by the reduction of thebaine in neutral solution and no doubt arose from the enol ether by hydrolysis during the isolation of the product.)... 

Thebainone-A enol methyl ether 154-156 Eton granules + 9-6 22 3... 

The reduction of thebaine with lithium aluminium hydride has been reexamined, and in the presence of aluminium chloride conditions have been found to give either thebainone-A enol methyl ether or neodihydrothebaine as the main product. Also obtained was a new base, isometathebainone enol methyl ether (86), identified by hydrolysis to isometathebainone (87), which gives... 

Dihydrothebainone [ix], obtained by the catalytic reduction of thebainone-A [v] [1] and thebainone-B [xm] [13], can be most conveniently prepared by the catalytic reduction of thebaine in acid solution [9-12, 25], and it can also be obtained by the hydrolysis of its two enol ethers (see below). It is a phenolic, ketonic, base, that shows the diazo-reaction in dilutions up to 1 in 2,000,000 [26-27], gives a methyl ether [28], oxime [9], semicarbazone [29], and a benzylidene [30] and piperonylidene [25] derivative. The optical antipode is produced by the sodium amalgam reduction of sinomenine [xxvi] and is known as desmethoxydihydrosinomenine [31]. 

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